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Titolo:
Reduced expression of Wnt-1 and E-cadherin, and diminished beta-catenin stability in MCF-7 breast cancer cells that overexpress protein kinase C-alpha
Autore:
Williams, CL; Noti, JD;
Indirizzi:
Guthrie Res Inst, Mol Biol Lab, Sayre, PA 18840 USA Guthrie Res Inst Sayre PA USA 18840 st, Mol Biol Lab, Sayre, PA 18840 USA Guthrie Res Inst, Mol Pharmacol Lab, Sayre, PA 18840 USA Guthrie Res InstSayre PA USA 18840 ol Pharmacol Lab, Sayre, PA 18840 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 6, volume: 19, anno: 2001,
pagine: 1227 - 1233
SICI:
1019-6439(200112)19:6<1227:REOWAE>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPITHELIAL-CELLS; CARCINOMA CELLS; PHORBOL ESTER; APOPTOSIS; PATHWAY; GROWTH; INHIBITION; ALPHA-V-BETA-3; METASTASIS; ACTIVATION;
Keywords:
beta-catenin; Wnt-1; E-cadherin; PKC-alpha; MCF-7; plakoglobin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Noti, JD Guthrie Res Inst, Mol Biol Lab, 1 Guthrie Sq, Sayre, PA 18840 USAGuthrie Res Inst 1 Guthrie Sq Sayre PA USA 18840 re, PA 18840 USA
Citazione:
C.L. Williams e J.D. Noti, "Reduced expression of Wnt-1 and E-cadherin, and diminished beta-catenin stability in MCF-7 breast cancer cells that overexpress protein kinase C-alpha", INT J ONCOL, 19(6), 2001, pp. 1227-1233

Abstract

MCF-7 breast cancer cells stably overexpressing protein kinase C-alpha (MCF-7-PKC-alpha cells) exhibit reduced cell-cell adhesion and increased tumorigenicity in nude mice. We investigated the possibility that alterations inE-cadherin and catenins contribute to the unique phenotype of MCF-7-PKC-alpha cells. Northern and Western blotting indicated that MCF-7-PKC-alpha cells express abnormally low amounts of plakoglobin mRNA and protein, and undetectable levels of E-cadherin mRNA and protein. In contrast, even though MCF-7-PKC-alpha cells express low levels of beta -catenin mRNA, they express undetectable levels of beta -catenin protein, suggesting that post-transcriptional events further diminish beta -catenin expression in these cells. Pulse-labeling of the cells with [S-35]methionine showed that the half-life of beta -catenin is less than 15 min in MCF-7-PKC-alpha cells, compared to over 2 h in MCF-7-Vector cells [MCF-7 cells transfected with pSV(2)M(2)6 vector only]. Incubation with LiCl to inactivate glycogen synthase kinase-3 (GSK-3) significantly prolonged the half-life of beta -catenin in MCF-7-PKC-alpha cells, suggesting that the GSK-3-dependent degradation of beta -catenin contributes to beta -catenin instability in these cells. Northern and Western blotting indicated that Wnt-1, which also inhibits GSK-3 activity, is expressed by MCF-7-Vector cells, but not by MCF-7-PKC-alpha cells. Transfection of (S37A)beta -catenin, which is resistant to GSK-3-dependent degradation, stimulated TCF/LEF-dependent luciferase expression from the pTOPFLASH reporter plasmid by 753-fold in MCF-7-PKC-alpha cells, and by 268-fold in MCF-7-Vector cells. Inactivation of GSK-3 by LiCl stimulated luciferase expression from the pTOPFLASH reporter plasmid by 12.4-fold in MCF-7-PKC-alpha cells, and by 4.8-fold in MCF-7-Vector cells, These results suggest that degradation of beta -catenin by GSK-3 contributes to beta -catenin instability in MCF-7-PKC-alpha cells, diminishing the ability of beta -catenin to actas a transcriptional co-activator. Reduced Wnt-1 expression by MCF-7-PKC-alpha cells may promote beta -catenin degradation by enhancing GSK-3 activity. Loss of beta -catenin-dependent cell-cell adhesion and transcription maycontribute to the aggressive phenotype of MCF-7-PKC-alpha cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 08:44:29